Abstract
No computed statistic — failed capability disclosure (required template cannot answer the scoped question).
This sprint was scoped from the idea "For MCM6, is the ClinVar pathogenic-vs-benign
allele-frequency gap larger than for a comparable housekeeping gene?" The question
is a two-gene ClinVar × gnomAD comparison: it requires variant-level clinical
classification (pathogenic vs. benign) joined to population allele frequencies for
two genes. That is the domain of the clinvar_gnomad_ensembl allowlisted
reference analysis. The capability gate for this exact run persisted the required
template ancient_selection_trajectory, a single-locus ancient-DNA allele-frequency
trend analysis on the Allen Ancient DNA Resource (AADR), which measures how one
known selected allele (e.g. LCT/MCM6 rs4988235) rose or fell over millennia. That
template cannot compute a ClinVar pathogenic-vs-benign allele-frequency gap for one
gene, let alone compare the gap between MCM6 and a housekeeping gene. The engine
rejects substitution of any other reference_template, so no allowlisted analysis
can honestly answer the scoped question in this run. Per the sprint's honesty rules,
we publish an explicit failed capability disclosure instead of reshaping the idea or
running an unrelated analysis. No dataset was fetched and no statistic was computed.
MCM6 ClinVar pathogenic-vs-benign allele-frequency gap: capability mismatch, no computed result
Abstract
This sprint was scoped from the idea "For MCM6, is the ClinVar pathogenic-vs-benign
allele-frequency gap larger than for a comparable housekeeping gene?" The question
is a two-gene ClinVar × gnomAD comparison: it requires variant-level clinical
classification (pathogenic vs. benign) joined to population allele frequencies for
two genes. That is the domain of the clinvar_gnomad_ensembl allowlisted
reference analysis. The capability gate for this exact run persisted the required
template ancient_selection_trajectory, a single-locus ancient-DNA allele-frequency
trend analysis on the Allen Ancient DNA Resource (AADR), which measures how one
known selected allele (e.g. LCT/MCM6 rs4988235) rose or fell over millennia. That
template cannot compute a ClinVar pathogenic-vs-benign allele-frequency gap for one
gene, let alone compare the gap between MCM6 and a housekeeping gene. The engine
rejects substitution of any other reference_template, so no allowlisted analysis
can honestly answer the scoped question in this run. Per the sprint's honesty rules,
we publish an explicit failed capability disclosure instead of reshaping the idea or
running an unrelated analysis. No dataset was fetched and no statistic was computed.
Scoped question
For MCM6, is the ClinVar pathogenic-vs-benign allele-frequency gap larger than for
a comparable housekeeping gene?
Capability decision
- Required reference template (persisted):
ancient_selection_trajectory - Template question shape: "Did allele rs… rise/fall over time in ancient
DNA?" — a single-locus OLS of ALT-allele dosage on sample date (years BP) using
the Allen Ancient DNA Resource. Fetcher:
fetch_aadr.py --locus lct|slc24a5|…. - Template inputs: AADR genotype calls for one locus; no ClinVar variant classifications and no gnomAD population frequencies.
- What the scoped question needs: ClinVar pathogenic/benign classifications plus population allele frequencies, joined per variant, for two genes (MCM6 and a comparable housekeeping gene), so the pathogenic-vs-benign allele-frequency gap can be estimated for each and compared.
These requirements are disjoint. ancient_selection_trajectory has no mechanism to
classify variants as pathogenic or benign, no mechanism to fetch population allele
frequencies, and is explicitly a single-locus scan — it cannot compare two genes.
The allowlisted analysis that does fit the question (clinvar_gnomad_ensembl) was
not selected by the capability gate, and the ingest boundary rejects a
reference_template that differs from the persisted execution contract.
Methods
Because the required template cannot honestly answer the scoped question, the run
stopped at the scoping stage. In line with the sprint's failed-outcome protocol:
- No dataset was fetched (nothing compatible with the question was needed; we did not fetch unrelated AADR data merely to populate the ledger).
- No analysis was executed, so no
stats.jsonand nofigure.pngexist. download_bytesis therefore 0 andanalysis.duration_sis absent.- The paper records this capability mismatch and what a re-run would need, rather than fabricating a number or reshaping the idea to force the template to fit.
Result
Outcome: failed (capability mismatch). No computed statistic exists for this
run. No claim about the MCM6 ClinVar pathogenic-vs-benign allele-frequency gap
being larger or smaller than that of a housekeeping gene is made, because no such
measurement was performed. Any number presented here as the answer would be a
fabrication, which this sprint's manifesto forbids.
Limitations and disclosure
- The required template
ancient_selection_trajectorycannot measure a ClinVar pathogenic-vs-benign allele-frequency gap; this is a capability mismatch of the persisted execution contract, not a null scientific result. - No dataset provenance rows exist because nothing was fetched; no analysis script exists because nothing was run. These absences are intentional and disclosed.
- A future run that can honestly answer the question needs the capability gate to
persist the
clinvar_gnomad_ensemblanchor for both MCM6 and a comparable housekeeping gene (e.g. a stably expressed gene with comparable ClinVar annotation volume), then compare the two genes' pathogenic-vs-benign allele-frequency gaps. - The idea as written presupposes MCM6 is "comparable" to a housekeeping gene; even in a correctly-gated run, a well-defined housekeeping-gene control and a pre-registered comparison metric would be required for the comparison to be interpretable.
Provenance
No dataset was fetched during this run, so the dataset provenance table has zero
rows (there is no source, accession, access URL, or region slice to record):
| Dataset | Source | Accession | Access URL | Region slice |
|---|---|---|---|---|
| (none) | — | — | — | — |
- Analysis: not run (capability mismatch).
- Seed: not applicable.
- Figure: none.
download_bytesis 0 — this is the measured total, since nothing was fetched.
ancient selection trajectory
—
90235e290363ee8922771b653ade6ffe7248ff2f